Composition for relieving stress, pharmaceutical composition and food and drink composition and method for relieving stress using the composition for relieving stress

ABSTRACT

A composition for relieving stress comprising a  Bifidobacterium breve  MCC 1274 (FERMBP-11175) as an active ingredient is provided. The composition for relieving stress according to the present technology can improve or prevent stress-induced anger, confusion, tension, or fatigue, or can improve vigor., stress can be assessed by POMS or POMS 2. The composition for relieving stress according to the present technology can be used for pharmaceutical compositions and food and drink compositions.

This application claims priority under 35 U.S.C. § 119 to JapanesePatent Application No. 2018-062467, filed Mar. 28, 2018, the entirety ofwhich is incorporated by reference herein.

BACKGROUND General Field

The present technology relates to a composition for relieving stress anda pharmaceutical composition, a food and drink composition, and a methodfor relieving stress using the composition for relieving stress.

Brief Description of the Related Art

In recent years, situations of mental stress and anxiety in daily lifeand work have been increasing. Mental stress causes psychologicalchanges such as anxiety, irritability and mental confusion, and if it isprolonged, there is a high possibility of causing depression andinterfering with interpersonal relationships. In addition, appetite maybe abnormally enhanced due to such mental stress, leading to obesity.

Until now, the use of chemical synthetic drugs such as tranquilizers,anti-anxiety agents and sleeping pills to relieve mental stress havealso been suggested. However, not all drugs are suitable for daily orlong-term use due to serious side effects and habits. As a way of copingwith mental stress, coping methods such as mental training and mindcontrol have been tried, but their effectiveness is limited.

In recent years, it has been clarified that the intestinal environmentis involved in signal transmission from the intestine to the brain, andstress control originating in the intestine has been reported.

For example, JP2014-101288 discloses an effect of suppressingstress-induced enteropathy, which comprises a sterilized form ofLactobacillus gasseri CP 2305 as an active ingredient.

Neurosci Lett. 2005 discloses that the parasympathetic activity isenhanced upon administration of Lactobacillus johnsonii Lal to rats.

JP2015-96542 discloses a vagus nerve activator containing cells ofLactobacillus gasseri CP 2305 as an active ingredient. WO2014/132982discloses a stress reducing agent containing Lactobacillus gasseri OLL2809, a probiotic lactic acid bacterium, as an active ingredient,reduces “tension-anxiety” in psychological profile examination andreduces “fatigue” by combining with α-LA.

Bioscience of Microbiota, Food and Health, 2015/1/21 discloses that thelactic acid bacteria beverage containing Bifidobacterium B. Bifidum Y asan active ingredient significantly improves “irritability” (anger) andmaintains “vigor” at a high level.

Journal of Bioengineering, Vol. 85, No. 12 521-526, 2007 reports thatintake of a lactic acid bacteria fermented tea beverage of Lactobacillusbrevis mh 4219 suppresses a decrease in “vigor” after stress loadcalculation.

Thus, although some improvement effects of psychological state byingesting probiotics cells or fermentation products have been reportedso far, probiotics are known to show different physiological effects ineach strain; and hence, no consistent results have been obtained in theabove report.

SUMMARY Problems to be Solved

As mentioned above, although some improvement effects of psychologicalstate by ingesting probiotics cells or fermentation products have beenreported so far, probiotics are known to show different physiologicaleffects in each strain; and hence, no consistent results have beenobtained in the above report.

Therefore, in the present technology, the main object is to provide anovel composition for relieving stress.

Means for Solving the Problems

Firstly, the present technology provides a composition for relievingstress comprising a Bifidobacterium breve MCC 1274 (FERMBP-11175) as anactive ingredient.

The composition for relieving stress according to the present technologycan improve or prevent stress-induced anger, confusion, tension, orfatigue, or can improve vigor.

In the present technology, stress can be assessed by POMS or POMS 2.

The composition for relieving stress according to the present technologycan be used for pharmaceutical compositions and food and drinkcompositions.

The present technology provides use of Bifidobacterium breve MCC 1274(FERMBP-11175) in a stress relieving agent, a drug for stress relieving,or a food/beverage for stress relieving; a method for relieving stress,comprising administering Bifidobacterium breve MCC 1274 (FERMBP-11175)to a subject; the method for relieving stress comprising administeringBifidobacterium breve MCC 1274 (FERMBP-11175) to a subject with normalbrain function; the method for relieving stress, comprisingadministering Bifidobacterium breve MCC 1274 (FERMBP-11175) to personover 35 years of age; the method for relieving stress, comprisingadministering Bifidobacterium breve MCC 1274 (FERMBP-11175) to a subjectfrom a period of autumn to winter; and use of Bifidobacterium breve MCC1274 (FERMBP-11175) for preventing, treating and/or improvingstress-induced migraine, tension headache, chronic pain, dizziness,Meniere's disease, menopausal disorder, Seasonal Affective Disorder(SAD), hyperthyroidism, organ asthma, hyperventilation syndrome, chronicobstructive pulmonary disease (COPD), chronic urticaria, shingles(herpes), atopic dermatitis, alopecia areata, hyperhidrosis,hypertension, angina pectoris, myocardial infarction, arrhythmia,orthostatic hypotension, temporomandibular joint arthrosis, stomatitis,functional gastrointestinal disorder, functional dyspepsia, gastricpain, gastroenteritis, diarrhea and constipation, gastric ulcer,duodenal ulcer, irritable bowel syndrome, ulcerative colitis,psychogenic vomiting, colic, night terror, night crying, rheumatoidarthritis, low back pain, muscle contraction headache, spasmodictorticollis, writer's cramp, eye strain, essential blepharospasm,nocturnal enuresis, overactive cystitis, psychogenic impotence, eatingdisorder or hyperphagia.

The present technology further provides a method for preventing,treating and/or improving stress-induced migraine, tension headache,chronic pain, dizziness, Meniere's disease, menopausal disorder,Seasonal Affective Disorder (SAD), hyperthyroidism, organ asthma,hyperventilation syndrome, chronic obstructive pulmonary disease (COPD),chronic urticaria, shingles (herpes), atopic dermatitis, alopeciaareata, hyperhidrosis, hypertension, angina pectoris, myocardialinfarction, arrhythmia, orthostatic hypotension, temporomandibular jointarthrosis, stomatitis, functional gastrointestinal disorder, functionaldyspepsia, gastric pain, gastroenteritis, diarrhea, constipation,gastric ulcer, duodenal ulcer, irritable bowel syndrome, ulcerativecolitis, psychogenic vomiting, colic, night terror, night crying,rheumatoid arthritis, low back pain, muscle contraction headache,spasmodic torticollis, writer's cramp, eye strain, essentialblepharospasm, nocturnal enuresis, overactive cystitis, psychogenicimpotence, eating disorder or hyperphagia by administeringBifidobacterium breve MCC 1274 (FERMBP-11175) to the subject.

According to the present technology, a novel composition for relievingstress can be provided.

Note that, the effect described here is not necessarily limited, and maybe any effect described in the present specification.

DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

Hereinafter, exemplary embodiments for implementing the presenttechnology will be described. Note that the embodiments described belowshow an example of a representative embodiment of the presenttechnology, and the scope of the present technology is not narrowlyinterpreted by this.

1. Composition for Relieving Stress

The composition for relieving stress of the present technology comprisesa Bifidobacterium breve MCC 1274 (FERMBP-11175) as an active ingredient.

Bifidobacterium breve MCC 1274 is deposited with National Institute ofAdvanced Industrial Science and Technology Patent MicroorganismsDepositary (Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan(Present IPOD National Institute of Technology and Evaluation—PatentOrganism Depositary (NITE-IPOD): 2-5-8120, Kazusakamatari, Kisarazu,Chiba

292-0818, Japan)) on Aug. 25, 2009 under the accession number IPODFERMBP-11175, and is generally available from the above storageinstitution.

Note that the names of the bacteria exemplified above are not limited tothe deposited strains which have been deposited or registered in apredetermined institution under the name of the bacteria, and includestrains (also called “derivative” or “derivative strain”) substantiallyidentical thereto. That is, “Bifidobacterium breve MCC 1274(FERMBP-11175)” is not limited to the strain deposited in the abovedepository under the deposit number of MCC 1274 (FERMBP-11175), andincludes substantially identical strains thereto.

With regards to the strain, “a strain substantially identical to theabove deposited strain” means a strain which belongs to the same speciesas the above deposited strain and from which the sleep promoting effect,which is the effect, can be obtained. The strain substantially identicalto the deposited strain may be, for example, a derivative having thedeposited strain as a parent strain. Derivative includes a strain bredfrom the deposited strain or a strain naturally produced from thedeposited strain.

The substantially identical strains and derivatives include thefollowing strains.

(1) A strain determined to be identical to the strain Bifidobacteriumbreve MCC 1274 by RAPD method (Randomly Amplified Polymorphic DNA) andPFGE method (Pulsed-field gel electrophoresis) described in Probioticsin food/Health and nutritional properties and guidelines for evaluation85 Page 43)(2) A strain that has only the gene derived fromBifidobacterium breve MCC1274, does not have a gene of foreign origin,and has 95% or more DNA identity with Bifidobacterium breve MCC1274(3) A strain bred from Bifidobacterium breve MCC 1274 (including strainbred by genetic engineering modification, mutation, natural mutation)and having a trait with MCC 1274

Bifidobacterium breve is one of strains belonging to the genusBifidobacterium. Bifidobacterium breve is mainly found in the largeintestine of infants, and known as an infant type Bifidobacteriumbacterium, along with Bifidobacterium longum subsp. Infantis and thelike are among the strains belonging to the genus Bifidobacterium.

The composition for relieving stress of this technology isBifidobacterium breve, the active ingredient of which predominantlyresides in the large intestine of infants and toddlers. Therefore, it ishighly safe and it is very useful because there is a lower risk of sideeffects even if it is continuously administered for a long period oftime. Furthermore, it is highly safe even when used in combination withother drugs.

Here, “relief” in the present specification means recovery of symptomsor disease, prevention or delay of deterioration of symptoms or disease,reversal, prevention or delay of progression of symptoms or disease, ortreatment of symptoms or disease, and the like. Furthermore, “relief” inthe present specification also includes the meaning of prevention.“Prevention” means preventing or delaying the onset of symptoms ordisease in a subject of application, or reducing the risk of onset ofsymptoms or disease in a subject of application or the like.

The composition for relieving stress of the present technology canrelieve stress, particularly in situations where brain function isexposed to stress in a normal state. Specifically, stress-induced anger,confusion or tension can be improved or prevented.

In the present technology, stress can be assessed by POMS (Profile ofMood States) or POMS 2 (Profile of Mood States 2nd Edition). POMS andPOMS 2 are registered trademarks of Multi-Health Systems Inc. Note thatthese psychological tests have different inspection methods depending onthe target population, such as for adults and adolescents, and differentnumber of question items at the time of examination, such as all itemsversion and short version. However, the inspection method and the numberof question items may be appropriately selected according to thesituation of the object.

Specifically, for example, in POMS, the factors of “Anger-Hostility(AH)”, “Confusion (C)”, “Depression-Dejection (DD)”, “Fatigue (F)”,“Tension-Anxiety (TA)”, “Vigor (V) and “Total Mood Disturbance (TMD)”are measured.

In POMS 2, the factors of “Anger-Hostility (AH)”,“Confusion-Bewilderment (CB)”, “Depression-Dejection (DD)”,“Fatigue-Inertia (FI)”, “Tension-Anxiety (TA)”, “Vigor-Activity (VA)”,“Friendliness (F)”, and “Total Mood Disturbance (TMD)” are measured.

The composition for relieving stress according to the present technologycan be used to prevent and/or treat symptoms and diseases that occurunder stress by relieving stress. Examples of the symptoms and diseasesthat occur under stress include migraine, tension headache, chronicpain, dizziness, Meniere's disease, menopausal disorder, SeasonalAffective Disorder (SAD), hyperthyroidism, organ asthma,hyperventilation syndrome, chronic obstructive pulmonary disease (COPD),chronic urticaria, shingles (herpes), atopic dermatitis, alopeciaareata, hyperhidrosis, hypertension, angina pectoris, myocardialinfarction, arrhythmia, orthostatic hypotension, temporomandibular jointarthrosis, stomatitis, functional gastrointestinal disorder, functionaldyspepsia, gastric pain, gastroenteritis, diarrhea and constipation,gastric ulcer, duodenal ulcer, irritable bowel syndrome, ulcerativecolitis, psychogenic vomiting, colic, night terror, night crying,rheumatoid arthritis, low back pain, muscle contraction headache,spasmodic torticollis, writer's cramp, eye strain, essentialblepharospasm, nocturnal enuresis, overactive cystitis, psychogenicimpotence, eating disorder or hyperphagia and the like.

The composition for relieving stress according to the present technologycan also be used to improve energy, vitality, concentration and the likeby relieving stress. That is, the composition for relieving stressaccording to the present technology can also be used as an energyimprover, a vitality improver, a concentration improver, and the like.

Furthermore, the composition for relieving stress according to thepresent technology can also relieve tension by relieving stress underspecific conditions. Specifically, for example, it may be used torelieve tension of the athlete during competition or relieve tensionduring tests and maintain the mental aspect under the situation thereof,and exert ordinary abilities.

The subject of the composition for relieving stress according to thepresent technology is not particularly limited, and can be applied toanimals including humans. Sex and age of the subjects are notparticularly limited, but for example, in the case of humans, thecomposition can be used particularly effectively for a person in middleor old age such as 35 years old or above, preferably 40 years old orabove, more preferably 45 years old or above. The composition can beused in infants and toddlers or children, in women during pregnancyperiod, perinatal period, lactation period and before and aftermenstruation.

Subjects to whom composition can be preferably administered are asfollows:

(1) A person who tends to be depressed, such as a person who ispunctual, serious, who has a strong sense of responsibility, ishardworking, has a strong sense of justice, who cannot refuse whenasked, who dislikes fighting with people, who always cares about whatother people think and the like(2) A person who is weak to environmental changes(3) A person who is sensitive to stress

The composition for relieving stress according to the present technologycan be used anytime throughout the year, but can be effectively usedparticularly in the period from autumn to winter when stress is likelyto occur, in the change of the season, and the like.

The composition for relieving stress according to the present technologymay contain a culture containing Bifidobacterium breve MCC 1274(FERMBP-11175) as its active ingredient Bifidobacterium breve MCC 1274(FERMBP-11175).

The medium for culturing Bifidobacterium breve used is not particularlylimited, and a medium usually used for culturing bacteria belonging tothe genus Bifidobacterium can be used.

That is, examples of a carbon source that can be used according toassimilability include saccharides such as glucose, galactose, lactose,arabinose, mannose, sucrose, starch, starch hydrolysate, molasses andthe like. Examples of a nitrogen source that can be used includeammonium salts and nitrates such as ammonia, ammonium sulfate, ammoniumchloride, ammonium nitrate and the like. Further, examples of theinorganic salts that can be used include sodium chloride, potassiumchloride, potassium phosphate, magnesium sulfate, calcium chloride,calcium nitrate, manganese chloride, ferrous sulfate and the like. Inaddition, organic components such as peptone, soybean powder, defattedsoybean meal, meat extract, and yeast extract may be used.

The culture conditions are not particularly limited as long as theeffects of the present technology are not impaired. For example, theculture temperature is usually from 25 to 50° C., and preferably from 35to 42° C. Moreover, culture is preferably cultivated under anaerobicconditions, for example, culture can be cultivated while ventilating ananaerobic gas such as carbon dioxide gas. Further, the culture may becultivated under slightly aerobic conditions such as liquid stationaryculture.

The culture obtained after culturing Bifidobacterium breve used may beused as it is, or may be used after dilution or concentration, or cellscollected from the culture may be used.

For present cells, the culture obtained after culturing may be used asit is, or may be used after dilution or concentration, or cellscollected from the culture may be used. In addition, various additionaloperations such as heating and lyophilization can be performed after theculturing as long as the effects are not impaired. In addition, thepresent cells may be live bacteria or dead bacteria. In the case of livebacteria, it is preferable to treat by the bacterial culture freezingmethod, the spray drying method, the lyophilization method, and the oildrop method. The dead bacteria include dead bacteria which aresterilized by heating, lyophilization and the like. Other methods forpreparing dead cells include a spray drying method, retort sterilizationmethod, lyophilization method, UHT sterilization method, pressuresterilization method, high pressure steam sterilization method, dry heatsterilization method, flow steam sterilization method, electromagneticwave sterilization method, electron beam sterilization method, microwavesterilization method, radiation sterilization method, ultraviolet raysterilization method, gaseous ethylene oxide sterilization method,gaseous hydrogen peroxide plasma sterilization method, chemicalsterilization method (alcohol sterilization method, formalin fixationmethod, electrolytic water treatment method) and the like. Also, thepresent cells may be crushed product. The crushed product may be oneobtained by crushing live bacteria or one obtained by crushing deadbacteria, or may be one subjected to heating or lyophilization aftercrushing. Further, crushing can be selected by, for example, physicalcrushing, enzymatic dissolution treatment, chemical treatment, autolysistreatment and the like using methods and equipment known in thetechnical field.

Physical crushing may be performed either in the form of a cellsuspension or in the form of a cell powder. As an example of physicalcrushing, crushing by stirring using ultrasonic homogenizer,homogenizer, ball mill, bead mill, dyno mill, planetary mill and thelike; crushing by pressure using a jet mill, French press, cellhomogenizer and the like; or crushing by damaging the cells by filterfiltration can be selected.

As the enzymatic dissolution treatment, for example, an enzyme such aslysozyme can be used to destroy the cell structure of the lactic acidbacterial cell.

As the chemical treatment, surfactants such as soybean phospholipid andglycerin fatty acid ester can be used to destroy the cell structure ofthe lactic acid bacterial cell.

As the autolysis treatment, lactic acid bacterial cells can be dissolvedby some enzymes of lactic acid bacteria themselves.

Note that, physical crushing is preferable because it is not necessaryto add other chemicals or compounds.

In the present specification, “culture” is a concept including culturesupernatant.

The composition for relieving stress according to the present technologymay consist only of the active ingredient or may be a composition inwhich the active ingredient and an optional ingredient other than theactive ingredient are blended.

The optional ingredient is not particularly limited, and additives (forexample, a pharmaceutical carrier or the like described later) which hasbeen conventionally blended in pharmaceuticals can be blended.

2. Specific Form of Composition for Relieving Stress According to thePresent Technology

The composition for relieving stress according to the present technologycan be used in the form of food and drink, pharmaceutical, quasi-drug,feed and the like.

Note that the application of the present embodiment may betherapeutically or non-therapeutically used.

“Non-therapeutic” is a concept that does not include medical practice,i.e., treatment of the human body by medical treatment. Examples thereofinclude health promotion, beauty practice and the like.

“Improvement” refers to the recovery from a disease, symptom orcondition; prevention or delay of deterioration of a disease, symptom orcondition; reversal, prevention or delay of the progression of a diseaseor symptom.

“Prevention” refers to preventing or delaying the onset of disease orsymptom in a subject of application, or reducing the risk of disease orsymptom in a subject of application or the like.

<Food and Drink>

The composition for relieving stress according to the present technologycan be prepared by adding it to known food and drink, or can be mixedinto the raw material of food and drink to produce new food and drink.

The food and drink using the composition for relieving stress accordingto the present technology may be in any form such as liquid, paste,solid, powder, and the like. In addition to tablet confectionery, liquidfood and the like, examples include wheat flour products, instant foods,processed agricultural products, processed marine products, processedmeat products, milk and dairy products, oils and fats, basic seasonings,combined seasonings and foods, frozen foods, confectionery, beverages,and other commercially available products and the like.

Examples of wheat flour products include bread, macaroni, spaghetti,noodles, cake mix, fried flour and bread crumbs and the like.

Examples of instant foods include instant noodles, cup noodles, retorts,cooked foods, cooked cans, microwave foods, instant soups and stews,instant miso soup and clear soup, soup cans, freeze-dried foods, andother instant foods and the like.

Examples of processed agricultural products include canned agriculturalproducts, canned fruits, jams and marmalades, pickles, boiled beans,dried agricultural products and cereals (grain processed food products)and the like.

Examples of processed marine products include canned marine products,fish ham/sausages, seafood paste products, fish delicacies, tsukudaniand the like.

Examples of processed meat products include meat cans/pastes, meat hamand sausages, and the like.

Examples of milk and dairy products include fermented milk such asyogurt, processed milk, milk drink, lactic acid bacteria drinks, cheese,ice creams, modified milk powders, cream, modified milk powder forinfants, nutritional supplementary food for infants, milk for pregnantwomen and lactating women, other dairy products and the like.

Examples of fats and oils include butter, margarine, vegetable oil andthe like.

Examples of basic seasonings include soy sauce, miso, sauces, tomatoprocessed seasoning, mirins, and vinegars and the like. Examples ofcombined seasonings and foods include cooking mixes, curry ingredients,sauces, dressings, noodles, spices, and other combined seasonings andthe like.

Examples of frozen foods include raw frozen food, semi-cooked frozenfood, cooked frozen food and the like.

Examples of confectionery include caramel, candy, chewing gum,chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japaneseconfectionery, rice cakes, bean sweets, dessert sweets, other sweets andthe like.

Examples of beverages include carbonated beverages, natural juices,fruit juices, soft drinks containing fruit juice, fruit pulp drinks,fruit drinks containing granules, vegetable drinks, soy milk, soy milkdrinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks,sports drinks, nutritional drinks, alcoholic beverages, other favoritebeverages and the like.

Examples of commercially available food other than the above includebaby food, Furikake (dried food sprinkled over rice), dried seasoningfor rice with tea and the like. The food and drink composition can bemanufactured by adding the present cells to the raw material of ordinaryfood and drink, and can be manufactured in the same manner as ordinaryfood and drink without adding the present cells. The present cells maybe added at any stage of the process of manufacturing the food and drinkcomposition. Moreover, the food and drink composition may bemanufactured through the fermentation process with the added cells.Examples of such food and drink composition include alactic-acid-bacteria drink, fermented milk and the like.

As a raw material of the food and drink composition, the raw materialused for ordinary food and drink can be used. The manufactured food anddrink composition can be taken orally.

Further, for example, for newborns or infants, it is also possible toadopt a method of adding the present cells to milked breast milk andorally ingested or ingested through a naso-gastric feeding tube or thelike.

In addition, the food and drink composition may use a component having aprobiotic effect known or to be found in the future or a component thatsupplements a probiotic effect as long as the effect is not impaired.For example, the food and drink composition can be produced by blendingpresent cells with components such as various proteins such as wheyprotein, casein protein, soybean protein, or pea protein or mixtures anddecomposition products thereof; amino acids such as leucine, valine,isoleucine or glutamine; vitamins such as vitamin B6 or vitamin C;creatine; citric acid; fish oil; or oligosaccharides such asisomaltooligosaccharides, galactooligosaccharides, xylooligosaccharides,soybean oligosaccharides, fructooligosaccharides, lactulose, and humanmilk oligosaccharides (HMO). Examples of the human milk oligosaccharidethat can be used include neutral human milk oligosaccharides such as2′-fucosyllactose, 3-fucosyllactose, 2′, 3-difucosyllactose,lacto-N-triose II, lacto-N-tetraose, lacto-N-neotetraose,lacto-N-fucopentaose I, lacto-N-neofucopentaose, 1-N-fucopentaose II,lacto-N-fucopentaose III, lacto-N-fucopentaose V,lacto-N-neofucopentaose V, lacto-N-difucohexaose I,lacto-N-difucohexaose II, 6′-galactosyl lactose, 3′-galactosyl lactose,lacto-N-hexaose and lacto-N-neohexaose; acidic human milkoligosaccharides such as 3′-sialyllactose, 6′-sialyllactose,3-fucosyl-3′-sialyllactose, disialyl-lacto-N-tetraose and the like.

As the food and drink according to the present technology, modified milkpowder can be mentioned. Modified milk powder refers to a modified milkpowder for children of 0 to 12 months, a follow-up milk for infantsafter 6 to 9 months and young children (up to 3 years old), a low birthweight modified milk powder for newborns weighing less than 2500 g atbirth (low birth weight infants), various therapeutic milks used for thetreatment of a child with a pathological condition such as milk allergyor lactose intolerance and the like. Furthermore, the composition can beapplied to health functional foods and foods for patients. The healthfunctional food system was established not only for ordinary foods butalso for food in the form of tablets, capsules and the like, based oninternal and external trends and consistency with the conventional foodsystem for specified health use. It consists of two types; a specialhealth food (individual permission type) and a nutrition functional food(standard type).

Food and drink according to the present technology may includenutritional supplementary food and milk for mothers during pregnancy andlactation. Milk for mothers refers to milk and the like which isbalancedly blended with the nutrition necessary for pregnancy andlactation.

Specifically, the formula milk can be produced, for example, by thefollowing method.

In other words, a method is provided for producing a powdered milk forinfants or a milk for mothers which comprises mixing a prebiotic and/orpowdered milk with a cell powder containing Bifidobacterium bacteria toobtain a powdered milk for stress relief

Specifically, for example, a method of producing powdered milk forstress relief is provided, which comprises the following steps (A) to(C):

(A) Culturing the Bifidobacterium bacteria in a medium containing a milkcomponent to obtain a culture;

(B) Subjecting the culture to spray drying and/or lyophilization toobtain cell powder; and

(C) Mixing the cell powder with prebiotics and/or powdered milk toobtain powdered milk for stress relief.

Further, the food composition may specifically be, for example, apowdered milk supplement for stress relief. For example, a powdered milksupplement for stress relief can be produced by the following method.

That is, a method is provided for producing a powdered milk supplementfor stress relief which comprises the following steps (A) and (B):

(A) Mixing the prebiotics, Bifidobacterium bacteria, and an excipient toobtain a mixture; and

(B) Tableting the resulting mixture.

The content of Bifidobacterium breve MCC 1274 (FERMBP-11175) in food anddrink according to the present technology can be freely set as long asthe effects of the present technology are not impaired., the content ofBifidobacterium breve MCC 1274 (FERMBP-11175) in food and drink isparticularly preferably 1×10³ to 1×10¹² cfu/g with respect to the finalcomposition of food and drink. The daily dose is at least 1×10³ cfu/dayor more, more preferably 1×10⁶ cfu/day or more, more preferably 1×10⁸cfu/day or more, furthermore preferably 2×10¹⁰ cfu/day or more, or it ispreferable to add more than the aforementioned dose. “cfu” representscolony forming unit. When the cells are dead, cfu/g or cfu/ml can bereplaced with individual cell/g or individual cell/ml. When the presentcell is a crushed product, it can be displayed in terms of weight fromthe number of cells (individual cell/g) before crushing.

Functional Indication Food and Drink

In addition, the food and drink as defined can be provided and sold as afood and drink for which a specific application (in particular, healthapplication) or a function is displayed.

“Display” act includes all acts to inform consumers about theapplication, and if it is an expression that can recall or analogize theapplication, regardless of the purpose of the display, the content ofthe display, the target object or medium to be displayed and the like,all fall under the “display” act of the present technology.

Moreover, it is preferable that “display” is expressed so that theconsumer recognizes the said application directly. Specifically,examples thereof include an act to assign, deliver, display for thepurpose of assignment or delivery, and import goods or packages of goodsrelating to the food and drink described by the application, an act todescribe, display or distribute the above application in anadvertisement, price list or transaction document concerning goods, orto describe the above application in information containing them andprovide it by an electromagnetic (internet or the like) method and thelike.

On the other hand, it is preferable that the display content is adisplay approved by the administration or the like (for example, adisplay which is approved based on various systems defined by theadministration and performed in a mode based on such an approval). Inaddition, it is preferable to affix such display contents to advertisingmaterials at sales sites such as packaging, containers, catalogs,pamphlets, POPs, and other documents.

In addition, “display” also includes display of health food, functionalfood, food for patients, enteral nutrition food, special purpose food,health functional food, special health food, functional display food,functional nutritional food, quasi-drugs and the like. Among these,examples of the display approved by the Consumer Affairs Agency includethe display approved by the Special health food system, the Functionaldisplay food system, the system similar to these and the like. Morespecifically, the display as special health food, the display asconditional special health food, the display as functional display food,the display of effects on the structure and function of the body,display of reducing disease risk and the like can be mentioned. Amongthese, typical examples include the special health food specified byHealth Promotion Act Enforcement Regulations (Apr. 30, 2003, Ministry ofHealth, Labor and Welfare Ordinance No. 86 of Japan) (particularlydisplay of the use of health), the functional display food specified byFood Labelling Law (2013 Law No. 70) and the display similar to these.

Note that the expression used in the display as described above is notlimited to only the expression of stress relief and the like. Even ifother expression is used, it is included in the scope of the presenttechnology as long as it indicates the effect of preventing, treatingand/or improving various diseases and symptoms related to stress relief.As such an expression, for example, it is also possible to display “tothose who are tired” and “to those who are stressed” based on variousapplications that make the consumer recognize the effect of stressrelief

<Pharmaceuticals, Quasi-Drugs>

The composition for relieving stress according to the present technologycan be prepared by adding it to a known pharmaceutical or quasi-drug(hereinafter, also referred to as “pharmaceutical or the like”), or itcan be mixed with raw materials such as pharmaceutical or the like toproduce new pharmaceutical and the like.

When the composition for relieving stress according to the presenttechnology is blended in a pharmaceutical or the like, thepharmaceutical or the like can be appropriately formulated into adesired dosage form according to an administration method such as oraladministration or parenteral administration. The dosage form is notparticularly limited, but in the case of oral administration, examplesinclude solid preparations such as powders, granules, tablets, trochesand capsules; and liquids such as solutions, syrups, suspensions andemulsions. In the case of parenteral administration, examples includesuppositories, sprays, inhalants, ointments, patches, injections and thelike., it is preferable to formulate into a dosage form for oraladministration.

Note that formulation can be carried out by known methods as appropriatedepending on the dosage form.

At the time of formulation, the formulation may be prepared byappropriately blending a formulation carrier. In addition to thecomposition for relieving stress of the present technology, it ispossible to use components such as excipients, pH adjusters, coloringagents, and flavoring agents that are generally used for formulation.Furthermore, it is also possible to use components in combination whichhave an effect of preventing, improving and/or treating diseases orsymptoms known or to be found in the future, according to the purpose.

Formulation carriers including various organic or inorganic carriers canbe used depending on the dosage form. Examples of the carrier in thecase of solid preparation include excipients, binders, disintegrants,lubricants, stabilizers, flavoring agents and the like.

Examples of the excipient include sugar derivatives such as lactose,sucrose, glucose, mannitol, sorbite, and the like; starch derivativessuch as corn starch, potato starch, α-starch, dextrin, carboxymethylstarch and the like; cellulose derivatives such as crystallinecellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose,carboxymethylcellulose, carboxymethylcellulose calcium and the like; gumarabic; dextran; pullulan; silicate derivatives such as light anhydroussilicic acid, synthetic aluminum silicate, magnesium aluminometasilicateand the like; phosphate derivatives such as calcium phosphate; carbonatederivatives such as calcium carbonate; sulfate derivatives such ascalcium sulfate and the like.

Examples of the binder include, in addition to the above-mentionedexcipients, gelatin; polyvinyl pyrrolidone; macrogol and the like.

Examples of the disintegrant include, in addition to the above-mentionedexcipients, chemically modified starch or cellulose derivatives such ascroscarmellose sodium, sodium carboxymethyl starch and crosslinkedpolyvinyl pyrrolidone.

Examples of the lubricant include talc; stearic acid; metal stearatessuch as calcium stearate, magnesium stearate and the like; colloidalsilica; waxes such as pea gum and spermaceti wax; boric acid; glycols;carboxylic acids such as fumaric acid and adipic acid; sodium salt ofcarbonic acid such as sodium benzoate; sulfates such as sodium sulfate;leucine; lauryl sulfates such as sodium lauryl sulfate and magnesiumlauryl sulfate; silicic acids such as anhydrous silicic acid and silicicacid hydrate; starch derivatives and the like.

Examples of the stabilizer include p-hydroxybenzoic acid esters such asmethylparaben and propylparaben; alcohols such as chlorobutanol, benzylalcohol and phenylethyl alcohol; benzalkonium chloride; aceticanhydride; sorbic acid and the like.

Examples of the flavoring agent include sweetening agents, acidulants,perfumes and the like.

Carrier to be used in the case of liquid drug for oral administrationincludes solvents such as water, flavoring agents and the like.

The content of Bifidobacterium breve MCC 1274 (FERMBP-11175) in thepharmaceutical and the like according to the present technology can befreely set as long as the effects of the present technology are notimpaired., the content of Bifidobacterium breve MCC 1274 (FERMBP-11175)in the pharmaceutical and the like is particularly preferably 1×10³ to1×10¹² cfu/g with respect to the final composition of the pharmaceuticaland the like. The daily dose is at least 1×10³ cfu/day or more, morepreferably 1×10⁶ cfu/day or more, more preferably 1×10⁸ cfu/day or more,furthermore preferably 2×10¹⁰ cfu/day or more, or the dose is preferablymore than the aforementioned dose.

<Feed>

The composition for relieving stress according to the present technologycan be prepared by adding it to a known feed, or can be mixed into rawmaterial of feed to produce new feed.

In the case of adding the composition for relieving stress according tothe present technology to feed, examples of the raw material of the feedinclude cereals such as corn, wheat, barley, rye; bran such as fusuma,wheat bran, rice bran, defatted rice bran; manufactured meals such ascorn gluten meal, corn jam meal and the like; animal feeds such asskimmed milk powder, whey, fish meal, bone meal; yeast such as beeryeast; mineral feeds such as calcium phosphate and calcium carbonate;oils and fats; amino acids; saccharides and the like. Moreover, the formof the feed includes the feed for pets (pet food and the like),livestock feed, fish feed and the like.

The content of Bifidobacterium breve MCC 1274 (FERMBP-11175) in the feedaccording to the present technology can be freely set according to theweight and the like as long as the effect of the present technology isnot impaired., the content of Bifidobacterium breve MCC 1274(FERMBP-11175) in the feed is particularly preferably 1×10³ to 1×10¹²cfu/g with respect to the final composition of feed. The daily dose isat least 1×10³ cfu/day or more, more preferably 1×10⁶ cfu/day or more,more preferably 1×10⁸ cfu/day or more, furthermore preferably 2×10¹⁰cfu/day or more, or the dose is preferably more than the aforementioneddose.

The present technology can also adopt the following configuration.

[1] A composition for relieving stress comprising a Bifidobacteriumbreve MCC 1274 (FERMBP-11175) as an active ingredient.

[2] The composition for relieving stress according to [1], whichimproves or prevents stress-induced anger, confusion, tension orfatigue, or improves vigor.

[3] The composition for relieving stress according to [2], wherein thestress is evaluated by POMS (Profile of Mood States) or POMS 2 (Profileof Mood States 2nd Edition).

[4] The composition for relieving stress according to any one of [1] to[3] is a pharmaceutical composition.

[5] The composition for relieving stress according to any one of [1] to[3] is a food and drink composition.

[6] Use of Bifidobacterium breve MCC 1274 (FERMBP-11175) as a stressrelieving agent, a drug for stress relief, or a food/drink for stressrelief.

[7] A method for relieving stress, comprising the administration ofBifidobacterium breve MCC 1274 (FERMBP-11175) to a subject.

[8] The method for relieving stress comprising the administration ofBifidobacterium breve MCC 1274 (FERMBP-11175) to a subject with normalbrain function.

[9] The method for relieving stress, comprising the administration ofBifidobacterium breve MCC 1274 (FERMBP-11175) to person over 35 years ofage.

[10] The method for relieving stress, comprising the administration ofBifidobacterium breve MCC 1274 (FERMBP-11175) to a subject from periodof autumn to winter.

[11] Use of Bifidobacterium breve MCC 1274 (FERMBP-11175) forpreventing, treating and/or improving stress-induced migraine, tensionheadache, chronic pain, dizziness, Meniere's disease, menopausaldisorder, Seasonal Affective Disorder (SAD), hyperthyroidism, organasthma, hyperventilation syndrome, chronic obstructive pulmonary disease(COPD), chronic urticaria, shingles (herpes), atopic dermatitis,alopecia areata, hyperhidrosis, hypertension, angina pectoris,myocardial infarction, arrhythmia, orthostatic hypotension,temporomandibular joint arthrosis, stomatitis, functionalgastrointestinal disorder, functional dyspepsia, gastric pain,gastroenteritis, diarrhea and constipation, gastric ulcer, duodenalulcer, irritable bowel syndrome, ulcerative colitis, psychogenicvomiting, colic, night terror, night crying, rheumatoid arthritis, lowback pain, muscle contraction headache, spasmodic torticollis, writer'scramp, eye strain, essential blepharospasm, nocturnal enuresis,overactive cystitis, psychogenic impotence, eating disorder orhyperphagia.

[12] A method for preventing, treating and/or improving stress-inducedmigraine, tension headache, chronic pain, dizziness, Meniere's disease,menopausal disorder, Seasonal Affective Disorder (SAD), hyperthyroidism,organ asthma, hyperventilation syndrome, chronic obstructive pulmonarydisease (COPD), chronic urticaria, shingles (herpes), atopic dermatitis,alopecia areata, hyperhidrosis, hypertension, angina pectoris,myocardial infarction, arrhythmia, orthostatic hypotension,temporomandibular joint arthrosis, stomatitis, functionalgastrointestinal disorder, functional dyspepsia, gastric pain,gastroenteritis, diarrhea, constipation, gastric ulcer, duodenal ulcer,irritable bowel syndrome, ulcerative colitis, psychogenic vomiting,colic, night terror, night crying, rheumatoid arthritis, low back pain,muscle contraction headache, spasmodic torticollis, writer's cramp, eyestrain, essential blepharospasm, nocturnal enuresis, overactivecystitis, psychogenic impotence, eating disorder or hyperphagia byadministering Bifidobacterium breve MCC 1274 (FERMBP-11175) to thesubject.

EXAMPLES

Hereinafter, the present technology will be described in more detailbased on examples. Note that the examples described below show anexample of a representative embodiment of the present technology, andthe scope of the present technology is not narrowly interpreted.

Example 1

<Preparing Test Sample>

The culture solution of Bifidobacterium breve MCC 1274 (FERMBP-11175)was concentrated and dried to obtain a live bacteria dry matter. Thelive bacteria dry matter was mixed with starch, and filled 345 mg into 1capsule to prepare a test sample.

On the other hand, a placebo capsule was prepared by filling only 345 mgof starch into a capsule, and used as a control sample.

It was confirmed that the test sample and the control sample wereindistinguishable in appearance, color and taste.

<Subject>

Healthy subjects of 20 years or older (BMI of 25 or more and less than30) were enrolled in the clinical trial as subjects. Furthermore,persons who did not violate the following exclusion criteria (1) to (7)were analyzed by body composition measurement, blood test, and interviewby consent.

(1) Person taking treatment for serious illness or person who has aserious past history of illness

(2) Person suffering from gastrointestinal disease and taking medication

(3) Person receiving drug treatment for lifestyle-related diseases(diabetes, hypertension, dyslipidemia)

(4) Person who has a past history of drug allergy or serious foodallergy

(5) Those who are pregnant, who intend to become pregnant during thetrial period, those who are breastfeeding

(6) Person who is heavy smoker, heavy drinker, and has irregularlifestyle

(7) Person who is judged to be unsuitable as a subject by theexamination doctor or study doctor based on the subject's background,physical findings, and interview results

Specific subject's background factors are shown in Table 1 below. Nosignificant difference was found in the age of the control group and thetest group.

TABLE 1 Difference Control group Test group between groups No. ofsubjects 40 40 N.S. (Person) Age (years old) 45.6 ± 8.5 45.4 ± 9.8 N.S.

<Test Method>

A randomized, double-blind, placebo-controlled, parallel-groupcomparison study was conducted. After a two-week pre-observation period,the subjects were assigned to a group receiving a control sample(hereinafter sometimes referred to as “control group”) and a groupreceiving a test sample (hereinafter sometimes referred to as “testgroup”). The subjects in both groups received the test sample or thecontrol sample once a day for 12 weeks together with water within 30minutes after meals. That is, the daily intake of the test group was 20billion live bacteria of Bifidobacterium breve MCC 1274 (FERMBP-11175).

Before intake, at 12 weeks after intake, in order to evaluate thetemporary mood state, the examination by “POMS 2 adult short version”,which is a mood profile examination, was carried out. As a result, thetotal scores were converted into T scores according to the Japanesemanual thereof. At the same time, for the test group, before intake andat 12 weeks after intake, the total score of seven factors: sleepquality, sleep onset time, sleep duration, sleep efficiency, sleepdifficulty, sleep medication use, and daytime awakening difficulties,were calculated using the Pittsburgh Sleep Quality Index (PSQI).

<Statistical Analysis>

The blind results were reviewed before the key open and analyzedexcluding those who did not meet the analysis criteria defined inadvance (i.e. those who meet less than 80% of the criteria, those whoviolate prohibited food or taking medicine, and others who seriouslyviolate or deviate from the study protocol). However, there were no suchindividuals in this study, so all 80 subjects were analyzed forefficacy.

<Results>

The results of the examination by “POMS 2 adult short version” are shownin Table 2 below. The average value and the variation of the overallscore of the Pittsburgh Sleep Quality Index (PSQI) in the test group areshown in Table 3 below.

TABLE 2 Control group Test group Before At 12 p Before At 12 p intakeweeks value* intake weeks value* Anger-Hostility 44.6 ± 6.1 46.9 ± 6.80.031 45.2 ± 6.6 46.3 ± 7.7 0.311 (AH) Confusion- 44.0 ± 6.7 47.1 ± 7.40.004 46.6 ± 8.7 46.6 ± 8.7 1.000 Bewilderment (CB) Depression- 45.2 ±5.7 46.8 ± 7.5 0.063 46.1 ± 7.5 47.0 ± 8.3 0.275 Dejection (DD)Fatigue-Inertia 43.6 ± 6.2 45.1 ± 6.9 0.189 44.7 ± 8.5 46.0 ± 8.6 0.077(FI) Tension-Anxiety 43.7 ± 5.4 45.4 ± 5.9 0.055 46.7 ± 9.7 46.8 ± 8.70.948 (TA) Vigor-Activity 49.4 ± 8.9 50.4 ± 8.0 0.358  52.6 ± 10.1  53.1± 11.0 0.673 (VA) Friendliness (F) 49.3 ± 8.6 51.9 ± 9.1 0.086  52.0 ±10.4  52.4 ± 11.4 0.767 Total Mood 44.3 ± 5.9 46.3 ± 6.7 0.032 45.3 ±8.4 46.0 ± 9.0 0.408 Disturbance (TMD) Result is shown in mean value andstandard deviation. *Intergroup comparison of mean value for beforeintake by unpaired t test

TABLE 3 Before intake After intake Variation 3.1 2.9 −0.2

Values of “Anger-Hostility (AH)”, “Confusion-Bewilderment (CB)”,“Depression-Dejection (DD)”, “Tension-Anxiety (TA)” and “Total MoodDisturbance (TMD)” shown in Table 2 were significantly increased at 12weeks compared to before intake in the control group, while these valuesremained low in the test group.

From these results, Bifidobacterium breve MCC 1274 (FERMBP-11175) wasshown to be effective in improving mood profile of “Anger-Hostility(AH)”, “Confusion-Bewilderment (CB)”, “Depression-Dejection (DD)”,“Tension-Anxiety (TA)” and “Total Mood Disturbance (TMD)”.

In addition, as shown in Table 3, the PSQI overall score was decreasedby −0.20 after intake for 12 weeks compared to before intake of the testsubstance, and sleep quality, sleep onset time, sleep duration, sleepefficiency, sleep difficulty, sleep medication use, and daytimeawakening difficulties were improved in a comprehensive manner.

Example 2

<Preparing Test Sample>

Fermented milk with or without Bifidobacterium breve strain MCC 1274(FERMBP-11175) was produced according to the following procedure.Firstly, a milk raw material, water as needed, other components and thelike were mixed, and subjected to the homogenization treatment and theheat sterilization treatment by a conventional method. Then, to theheat-sterilized modified milk liquid, a lactic starter and afreeze-dried powder of Bifidobacterium breve strain MCC1274(FERMBP-11175) were added (inoculated) and fermented by maintaining at apredetermined fermentation temperature. When the pH reached to thetarget value, the curd formed was crushed by stirring and cooled to 10°C. or less to produce a fermented milk. This was used as a test sample.

On the other hand, in the same process, the fermented milk in which onlythe lactic starter was added (inoculated) to the modified milk liquidwas produced. This was used as a control sample.

It was confirmed that the test sample and the control sample wereindistinguishable in appearance, color and taste.

<Subject>

Healthy subjects between the ages of 20 and 65 at the time of consent(BMI 25 of or more and less than 30) were enrolled in the clinical trialas subjects. Furthermore, 140 persons who did not violate the followingexclusion criteria (1) to (6) were selected as subjects according tobody composition measurement, blood test, and interview by doctor.

(1) Person who has a past history such as serious disease

(2) Person receiving drug treatment for lifestyle-related diseases(diabetes, hypertension, dyslipidemia)

(3) Person who has drug allergy or serious food allergy

(4) Those who are pregnant, who intend to become pregnant during thetrial period, those who are breastfeeding

(5) Person who is a heavy smoker and a heavy drinker

(6) Person who is judged to be unsuitable as a subject by theexamination doctor or study doctor based on the subject's background,physical findings, and interview results

Specific subject's background factors are shown in Table 4 below. Nosignificant difference was found in the age of the control group and thetest group.

TABLE 4 Difference Control group Test group between groups No. ofsubjects 70 70 N.S. (Person) Age (years old) 46.8 ± 8.7 47.6 ± 8.6 N.S.

<Test Method>

A randomized, double-blind, placebo-controlled, parallel-groupcomparison study was conducted. After a two-week pre-observation period,140 subjects were assigned to a group receiving a control sample(hereinafter sometimes referred to as “control group”) and a groupreceiving a test sample (hereinafter sometimes referred to as “testgroup”). Each group had 70 subjects. The subjects in both groupsreceived the test sample or the control sample once a day after mealsirrespective of breakfast, lunch or dinner for 12 consecutive weeks. Theviable count of Bifidobacterium breve MCC 1274 (FERMBP-11175) containedin the test sample was at least 100 million per day (one dose). That is,the daily intake of the test group was at least 100 million livebacteria of Bifidobacterium breve MCC 1274 (FERMBP-11175).

Before intake, at 12 weeks after intake, in order to evaluate thetemporary mood state, the examination by “POMS 2 adult short version”,which is a mood profile examination, was carried out. As a result, thetotal scores were converted into T scores according to the Japanesemanual thereof

<Statistical Analysis>

The blind results were reviewed before the key open and analyzedexcluding those who did not meet the analysis criteria defined inadvance (i.e. those who meet less than 80% of the criteria, those whoviolate prohibited food or taking medicine, and others who seriouslyviolate or deviate from the study protocol). However, there were no suchindividuals in this study, so all 140 subjects were analyzed forefficacy.

<Results>

The results of the examination by “POMS 2 adult short version” are shownin Table 5 below.

TABLE 5 TMD T score AH CB DD FI TA VA F score Test group 0.1 −0.3 0.1−0.4 −0.5 1.2 0.3 −0.4 Control 1.7 1.9 1.1 0.6 1.8 −0.1 0.0 1.5 group pvalue (t- 0.10 0.01 0.24 0.33 0.03 0.32 0.82 0.03 test)

Values of “Anger-Hostility (AH)”, “Confusion-Bewilderment (CB)”,“Depression-Dejection (DD)”, “Fatigue-Inertia (FI)”, “Tension-Anxiety(TA)” and “Total Mood Disturbance (TMD)” shown in Table 5 were lower inthe test group compared to the control group. Particularly,“Confusion-Bewilderment (CB)”, “Tension-Anxiety (TA)” and “Total MoodDisturbance (TMD)” showed low value with a significant difference.

The values of “Vigor-Activity (VA)” and “Friendliness (F)” were high inthe test group compared to the control group.

From these results, Bifidobacterium breve MCC 1274 (FERMBP-11175) wasshown to be effective in improving all mood profiles of “Anger-Hostility(AH)”, “Confusion-Bewilderment (CB)”, “Depression-Dejection (DD)”,“Fatigue-Inertia (FI)”, “Tension-Anxiety (TA)”, “Total Mood Disturbance(TMD)”, “Vigor-Activity (VA)” and “Friendliness (F)”.

Preparation Example

The preparation example of the pharmaceutical composition and the foodcomposition for stress relief is shown as follows.

Preparation Example 1

Bifidobacterium breve MCC 1274 (FERMBP-11175) was added to 3 mL of MRSliquid medium, anaerobically cultured at 37° C. for 16 hours. Theculture solution was then concentrated, and freeze-dried to obtainfreeze-dried powder of bacteria (bacterial cell powder). The bacterialcell powder, the whey protein concentrate (WPC), and the prebiotics(lactulose, raffinose and galactooligosaccharide) were homogeneouslymixed to obtain a composition. 20 g of the composition was dissolved in200 g of water to obtain a composition for relieving stress.Administration of the resulting composition can alleviate the stress.

Preparation Example 2

Bifidobacterium breve MCC 1274 (FERMBP-11175) was added to 3 mL of MRSliquid medium, and anaerobically cultured at 37° C. for 16 hours. Theculture solution was then concentrated and freeze-dried to obtainfreeze-dried powder of bacteria (bacterial cell powder). The bacterialcell powder, the dry powder of milk protein concentrate (MPC 480,manufactured by Fontera Co., 80 mass % protein content, caseinprotein:whey protein=about 8:2), and the prebiotics (lactulose,raffinose and galactooligosaccharide) were homogeneously mixed to obtaina composition. 20 g of the composition was dissolved in 200 g of waterto obtain a composition for relieving stress. Administration of theresulting composition can alleviate the stress.

Preparation Example 3

Bifidobacterium breve MCC 1274 (FERMBP-11175) was added to 3 mL of MRSliquid medium, anaerobically cultured at 37° C. for 16 hours. Theculture solution was then concentrated and freeze-dried to obtainfreeze-dried powder of bacteria (bacterial cell powder). Next,prebiotics (lactulose, raffinose and galactooligosaccharide) andcrystalline cellulose were charged into a stirring granulator and mixed.Thereafter, the purified water was added to granulate. Resultinggranules were dried to obtain granules (pharmaceutical composition)containing an extract of bacteria and prebiotics and containing anexcipient. Administration of the granules can alleviate the stress.

Preparation Example 4

The preparation method of fermented milk to which Bifidobacterium breveMCC 1274 (FERMBP-11175) was added is shown below.

Firstly, the milk raw material, the water as needed, other componentsand the like were mixed, and preferably subjected to homogenizationtreatment and heat sterilization treatment. The homogenization treatmentand the heat sterilization treatment can be performed by a conventionalmethod. Then, to the heat-sterilized modified milk liquid, a lacticstarter was added (inoculated) and fermented by maintaining at apredetermined fermentation temperature to obtain a fermented product.The curd was formed by fermentation.

Examples of the lactic starter that can be used include the lactic acidbacteria usually used for producing yogurt, such as Lactobacillusbulgaricus, Lactococcus lactis, Streptococcus thermophilus. When the pHreached the target value, the curd formed was crushed by stirring andcooled to 10° C. or less to produce a fermented product. This was usedas a test sample. By cooling to 10° C. or less, the activity of lacticacid bacteria can be reduced to suppress the production of an acid.

Next, the fermented product obtained in the fermentation step wassubjected to heat treatment to obtain a fermented product after heating(fermented product after heat treatment). By appropriately heating thefermented product, it is possible to suppress the production of acid bylactic acid bacteria in the fermented product after heating. Thus, it ispossible to suppress a decrease in pH during the subsequentmanufacturing step and/or during storage of the concentrated fermentedmilk containing Bifidobacterium; as a result, it is possible to improvethe survivability of Bifidobacterium.

Thereafter, to the fermented product obtained in the heat treatment stepafter heating, Bifidobacterium breve MCC 1274 (FERMBP-11175) andprebiotics (lactulose, raffinose and galactooligosaccharide) were added.The amount of Bifidobacterium breve MCC 1274 (FERMBP-11175) added to thefermented product after heating is preferably from 1×10⁷ to 1×10¹¹cfu/ml, more preferably from 1×10⁸ to 1×10¹⁰ cfu/ml. WhenBifidobacterium breve MCC 1274 (FERMBP-11175) is dead, cfu/mL can bereplaced with individual cells/mL.

The fermented product after heating was concentrated after addingBifidobacterium breve MCC 1274 (FERMBP-11175) and prebiotics thereto.The concentration step can be performed using a known concentrationmethod as appropriate. For example, centrifugation method or membraneseparation can be used. In the centrifugation method, whey in thesubstance to be concentrated (fermented product after heating to whichbifidobacteria and prebiotics have been added) is removed to obtainconcentrated fermented milk containing bifidobacteria and prebioticswith an increased solid content concentration.

Administration of the fermented milk obtained as described above canalleviate stress.

Preparation Example 5

The preparation method of modified milk powder to which Bifidobacteriumbreve MCC 1274 (FERMBP-11175) was added is shown below.

10 kg of desalted milk whey protein powder (manufactured by Mirai), 6 kgof milk casein powder (manufactured by Fontera), 48 kg of lactose(manufactured by Mirai), 920 g of mineral mixture (manufactured byTomita Pharmaceutical Co., Ltd), and 32 g of vitamin mixture(manufactured by Tanabe Seiyaku Co., Ltd.), 500 g of lactulose(manufactured by Morinaga Milk Industry Co., Ltd.), 500 g of raffinose(manufactured by Nippon Tensai Seito Co., Ltd.) and 900 g ofgalactooligosaccharide liquid sugar (manufactured by YakultPharmaceutical Co., Ltd.) were dissolved in 300 kg of warm water. Themixture was further heated at 90° C. for 10 minutes and dissolved and 28kg of prepared fat (manufactured by Taiyo Yushi Co., Ltd.) was added andhomogenized. Thereafter, the mixture was sterilized and concentrated andspray-dried to prepare about 95 kg of modified milk powder. To this, 100g of bacterial cell powder (1.8×10¹¹ cfu/g, manufactured by MorinagaMilk Co., Ltd.) of Bifidobacterium breve MCC 1274 (FERMBP-11175)dispersed in starch was added, to prepare about 95 kg ofBifidobacterium-oligosaccharide-blended modified milk powder. When themodified milk powder was dissolved in water to form modified milk liquidhaving a total solid concentration of 14% (w/V), which is a standardmilk formula concentration, the number of Bifidobacterium in themodified milk liquid obtained was 2.7×10⁹ cfu/100 mL. Administration ofmodified milk powder obtained as described above can alleviate stress.

1. A composition for relieving stress comprising a Bifidobacterium breveMCC 1274 (FERMBP-11175) as an active ingredient.
 2. The composition forrelieving stress according to claim 1, which improves or preventsstress-induced anger, confusion, tension or fatigue, or improves vigor.3. The composition for relieving stress according to claim 1, whereinstress is evaluated by POMS (Profile of Mood States) or POMS 2 (Profileof Mood States 2nd Edition).
 4. The composition for relieving stressaccording to claim 1 is a pharmaceutical composition.
 5. The compositionfor relieving stress according to claim 1 is a food and drinkcomposition.
 6. Use of Bifidobacterium breve MCC 1274 (FERMBP-11175) asa stress relieving agent, a drug for stress relief, or a food/drink forstress relief.
 7. A method for relieving stress, comprising theadministration of Bifidobacterium breve MCC 1274 (FERMBP-11175) to asubject.
 8. The method for relieving stress of claim 7, wherein thesubject has normal brain function.
 9. The method for relieving stress ofclaim 7, wherein said subject is a person over 35 years of age.
 10. Themethod for relieving stress of claim 7, wherein said administering is toa subject from a period of autumn to winter.
 11. Use of Bifidobacteriumbreve MCC 1274 (FERMBP-11175) for preventing, treating and/or improvingstress-induced migraine, tension headache, chronic pain, dizziness,Meniere's disease, menopausal disorder, Seasonal Affective Disorder(SAD), hyperthyroidism, organ asthma, hyperventilation syndrome, chronicobstructive pulmonary disease (COPD), chronic urticaria, shingles(herpes), atopic dermatitis, alopecia areata, hyperhidrosis,hypertension, angina pectoris, myocardial infarction, arrhythmia,orthostatic hypotension, temporomandibular joint arthrosis, stomatitis,functional gastrointestinal disorder, functional dyspepsia, gastricpain, gastroenteritis, diarrhea and constipation, gastric ulcer,duodenal ulcer, irritable bowel syndrome, ulcerative colitis,psychogenic vomiting, colic, night terror, night crying, rheumatoidarthritis, low back pain, muscle contraction headache, spasmodictorticollis, writer's cramp, eye strain, essential blepharospasm,nocturnal enuresis, overactive cystitis, psychogenic impotence, eatingdisorder or hyperphagia.
 12. A method for preventing, treating and/orimproving stress-induced migraine, tension headache, chronic pain,dizziness, Meniere's disease, menopausal disorder, Seasonal AffectiveDisorder (SAD), hyperthyroidism, organ asthma, hyperventilationsyndrome, chronic obstructive pulmonary disease (COPD), chronicurticaria, shingles (herpes), atopic dermatitis, alopecia areata,hyperhidrosis, hypertension, angina pectoris, myocardial infarction,arrhythmia, orthostatic hypotension, temporomandibular joint arthrosis,stomatitis, functional gastrointestinal disorder, functional dyspepsia,gastric pain, gastroenteritis, diarrhea, constipation, gastric ulcer,duodenal ulcer, irritable bowel syndrome, ulcerative colitis,psychogenic vomiting, colic, night terror, night crying, rheumatoidarthritis, low back pain, muscle contraction headache, spasmodictorticollis, writer's cramp, eye strain, essential blepharospasm,nocturnal enuresis, overactive cystitis, psychogenic impotence, eatingdisorder or hyperphagia by administering Bifidobacterium breve MCC 1274(FERMBP-11175) to the subject.